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䡵 Karoshi (Death from Overwork)
Work and Ischemic Heart Disease
JMAJ 47(5): 216–221, 2004
Professor, Internal Medicine II, Saitama Medical School
Abstract: Recent studies provide convincing evidence that work-related stress
contributes significantly to the pathogenesis and onset of ischemic heart disease.
Work-related stress is one of the most widely studied chronic life stresses related
to ischemic heart disease. Many factors in the work environment have been studied
in relation to the development of ischemic heart disease. One model proposed
based on studies of tension at work is the “job strain” model, defined by Karasek
as jobs with high demand but low decision latitude. Hyperresponsivity of the sympathetic nervous system is manifested by an exaggerated heart rate and blood
pressure responses to work-related stress. Like other psychosocial factors, chronic
work-related stress appears to have direct pathophysiological effects, including
stimulation of the hemodynamic system and neurohumoral arousal. However, the
data have indicated the existence of individual differences in responsivity of the
sympathetic nervous system. Acute stress triggers myocardial ischemia, promotes
arrhythmogenesis, and stimulates platelet function, and in the presence of underlying atherosclerosis, it causes coronary vasoconstriction. Because multiple coronary risk factors, including previously established factors such as hypertension,
hypercholesterolemia, and smoking, as well as work-related stress, contribute to
the development of ischemic heart disease, worker-specific targeted interventions
are necessary.
Key words: Work-related stress; Ischemic heart disease;
Sympathetic nervous system; Psychosocial factors;
Coronary risk factors
Ischemic heart disease pursues a course that
starts with diffuse intimal thickening of the
coronary arteries in adolescence, with symp-
toms developing in the final stage, coronary
arteriosclerosis, which progresses through complex interactions between cells over a long
period. In addition to genetic constitution, lifestyle and environmental factors affect its onset
This article is a revised English version of a paper originally published in
the Journal of the Japan Medical Association (Vol. 128, No. 6, 2002, pages 875–879).
The Japanese text is a transcript of a lecture originally aired on May 24, 2002, by the Nihon Shortwave
Broadcasting Co., Ltd., in its regular program “Special Course in Medicine”.
JMAJ, May 2004—Vol. 47, No. 5
Workplace stressors
Personal factors (2)
Working long hours
Other aspects of employment
Personal factors (1)
Irregular work
Long work hours
Shift-work/night work
Work involving a great deal
of travel
Work proficiency
Work associated with
psychological stress
Alcohol consumption, smoking,
obesity, neglect of health
Underlying diseases
Inadequate health efforts
Poor health care/
seeking of medical care
Stress response/fatigue
Psychological responses:
Work environment
Job dissatisfaction
Physiological responses:
time-zone differences
Blood pressure/heart rate
Unusual events
of fatigue
Heart disease
Non-workplace stressors
Housework, staying up late
at night
Family relations, relations
with friends
Relaxing factors
Social support/
Stress countermeasures
Relaxing factors
Financial problems
environmental problems
Partially related factors
Unusual events
Fig. 1 Work-related stress/relaxation factors and ischemic heart disease
(Partial revision of the Occupational Stress Model of the United States National Institute of Occupational Safety and Health)
(Wada, O.: Work and heart disease — Risk factors for “Karoshi (death from overwork)”
and preventive measures. Quoted from Sangyo Igaku Review 2002; 4: 186)
and progression. Clinical factors related to the
onset and progression of coronary artery disease have been elucidated based on epidemiological studies, including the Framingham
Study, and they are referred to by the general
term “coronary risk factors”.
Subsequent studies have shown that stress is
also a coronary risk factor. Models that consider worker stress based on three types of
stressors: 1) workplace stressors, 2) non-workplace stressors, and 3) personal factors, and the
opposite, relaxing factors that relieve stress,
have been proposed to evaluate worker stress
(Fig. 1).1) In some cases of ischemic heart disease some of these factors, such as amount of
work and nature of the work, are thought to
play a major role in the onset of the disease as
stressors in the workplace. The social medicine
term “Karoshi (death from overwork)” has
come into widespread use and has attracted
the attention of the public. In other cases of
ischemic heart disease, in particular, an acute
onset occurs in an asymptomatic worker and
pursues a course leading to sudden death, giving the family the impression of a disease of the
acute onset type. Thus, ischemic heart disease
possesses aspects that make it easy to view as a
disease associated with industrial accidents.
In this paper I will outline the associations
between stress according to type and aspects of
work and ischemic heart disease in workers by
dividing it into 1) relatively long-term effects
and 2) stressors immediately before the onset
that act as a trigger.
JMAJ, May 2004—Vol. 47, No. 5
Table 1 Relative Risk of Multiple Risk Factors for Ischemic Heart Disease
(Model based on the results of the Framingham survey)
Relative risk of multiple risk factors for developing coronary artery disease over a 10- year period (men)
Risk factor
Present (Ⳮ)/Absent (ⳮ)
Hypertension (systolic pressure욷160 mmHg)
High cholesterol (욷250 mg/dl)
Low HDL-cholesterol (쏝35 mg/dl)
Left ventricular hypertrophy (by ECG)
Relative risk
Onset of Ischemic Heart Disease
1. Definition of ischemic heart disease
In ischemic heart disease the oxygen supply
becomes insufficient to meet the demands of
the myocardium because of lesions in the coronary arteries, and as a result the myocardium
becomes hypoxic (ischemic), and myocardial
function is impaired. The term “coronary artery
disease” is used when there are lesions in the
coronary arteries, but symptoms due to myocardial ischemia or demonstration of myocardial ischemia are not always necessary to make
the diagnosis. “Ischemic heart disease” is a diagnostic category based on functional abnormalities that develop as a result of myocardial
ischemia, and “coronary artery disease” is a
diagnostic term that depends on whether morphological abnormalities are present in the
coronary arteries.
2. Progression of atherosclerosis and
the onset of ischemic heart disease
“Arteriosclerosis” is a general pathological
term used to describe pathological sclerosis
and thickening of arterial walls. Based on their
pathological characteristics, coronary arteriosclerosis, some cerebral infarctions, and occlusive arteriosclerosis of peripheral arteries are
classified under atherosclerosis.
According to pathology studies, it is now
JMAJ, May 2004—Vol. 47, No. 5
known that diffuse intimal thickening is observed in the coronary arteries in childhood
and adolescence, and the thickening is said to
be the basis for the development of coronary
disease in later years. The lipid-rich plaques of
atherosclerotic lesions cause ruptures and fissures, and vessel-obstructing thrombi form and
are thought to cause the onset of acute myocardial infarction and sudden cardiac death.
Risk Factors for Arteriosclerosis
1. Outline of coronary risk factors
The chief uncorrectable risk factors are age,
gender, and family history. The correctable risk
factors include hyperlipidemia, hypertension,
smoking, diabetes, and obesity, with three of
them, hyperlipidemia, hypertension, and smoking, constituting the greatest risk factors. The
impact of the risk factors varies with the pathological type of arteriosclerosis. Hypertension is
the greatest risk factor for arteriolosclerosis,
whereas hyperlipidemia contributes more to
atherosclerosis. Recent studies have shown
that high serum Lp (a) values, elevated homocysteine values, and high CRP values are also
risk factors.
2. Impact of arteriosclerosis risk factors and
their evaluation
The impact of arteriosclerosis risk factors in
each individual varies with the strength of the
effect of each factor, its duration, timing of its
effect, sensitivity and reactivity of the individual, etc. Arteriosclerosis develops when a
coronary risk factor acts in addition to a genetic
constitution, and when more than one risk
factor is present, the risk of developing arteriosclerosis has been found to increase in an additive manner (Table 1).2)
Occupational Factors
1. Work time
Based on previous studies, correlations have
been reported between long work hours and
the prevalence rate of blood pressure elevation
and heart disease. The following are suspected
of being reasons why long work hours have an
impact on cerebrovascular and cardiovascular
disease: 1) sleep time is insufficient, and fatigue
builds up, 2) decreased breaks and rests during off-work hours and decreased time for leisure activities, 3) the stress imposed by having
to marshal mental and physiological functions
decreased by fatigue and maintain the constant
level demanded by the job when hours are
long, and 4) increased time in contact with
work-related stressors.
One of these factors, lack of sleep, is thought
to increase the responsiveness of the sympathetic nervous system and the prevalence rate
of heart disease.3) In a study on the acute effects
of short sleep time, significant increases in
blood pressure and heart rate were observed at
sleep times of 3–4 hours a day. There is also a
report claiming a 2.08 times higher mortality
rate from ischemic heart disease at sleep times
under 4 hours a day than when sleep lasted 7–
7.9 hours. In addition, morbidity and mortality
from stroke and heart disease have been shown
to rise in sleep-deficient states with sleep times
under 4–6 hours a day for long periods.3)
2. Irregular work hours
Irregular work hours interfere with the sleepwakefulness rhythm and cause deterioration of
the rhythm of daily living. Moreover, irregular
shift-work hours entail the possibility of never
being able to take a complete rest. Persons with
occupations associated with irregular work
hours include transportation workers, such as
taxi and truck drivers, guards, and medical personnel on call.
The results of research on shift work and the
development of heart disease suggests that the
relative risk is 1.2–1.5 times greater, and shiftwork hours, frequency, night-work time frame,
work intervals, etc., are thought to affect the
aggravation by shift work.
However, when shift work is performed
according to schedule as routine work or when
routine work is in a night-work time frame, the
stress experienced can also be considered to
fall within the range of the stress in ordinary
life. Long work hours and work that involves a
great deal of travel may also have an impact on
the cardiovascular system.3)
3. Work environment
Hot environments are thought to subject
the circulatory system to considerable stress,
but there have been no data showing a direct
association with increased mortality from heart
disease, and dehydration may be a factor that
triggers its onset. Elevation of blood pressure
have been observed during exposure to noise,
and there has even been a report describing an
association between the onset of ischemic heart
disease and noise, but no conclusion has been
drawn that it is a risk factor.3)
4. Work associated with mental stress
(1) Effect of mental strain on the circulatory
Changes in the circulatory system due to
stress develop as a result of activation of the
amygdalo-sympathetic-adrenomedullary system.
Its response has been found to consist of blood
pressure elevation, increased heart rate, increase in free fatty acids due to an increase in
noradrenaline in the blood, and blood glucose
elevation. Chronic persistence of this response
JMAJ, May 2004—Vol. 47, No. 5
is thought to have an effect on the progression
of coronary arteriosclerosis mediated by risk
factors.4) In earlier research blood pressure
elevations while at work were reported to be
mild. Moreover, while many cohort studies
examining work-related stress and the incidence of ischemic heart disease have reported
an increased relative risk, other research data
have shown no difference, and no consensus
has been reached.4)
Several stress models have been proposed
as methods of evaluating the mental stress
of work. The job strain model proposed by
Karasek and colleagues features a high level of
mental strain, low job decision latitude, and
little support in society or at work, and a tendency for high levels of stress to develop and
an increased relative risk of onset of ischemic
heart disease have been shown in so-called “highdemand, low-freedom, low-support” work.1,5)
Generally speaking, there are often large individual differences in response to stress, with
the degrees and patterns of response to external factors differing, and medical evaluation of
whether acute stage reactions are associated
with a significant increase in rate of occurrence
of chronic disease, etc., is often difficult.
(2) Occupation/job classification and ischemic
heart disease1)
In a study examining the relationship between
the onset of stroke and heart diseases and occupation/job classification, associations were reported to have been found with bus and taxi
drivers and other motor vehicle drivers, administrative workers, physicians, guards, etc.3)
There are also reports that indicate an association between work-related stress and blood
pressure elevation and reports that do not.
Some studies have shown that systolic blood
pressure elevations of 4–12 mmHg and diastolic
blood pressure elevations of 2.8–4.3 mmHg
while working. However, many of the studies
that examined the association between workrelated stress and the occurrence of cardiovascular disease over a long period have found low
relative risk levels of 1–2.3)
JMAJ, May 2004—Vol. 47, No. 5
5. Personality traits and ischemic heart
Associations between personality traits and
ischemic heart disease have been investigated
by focusing on factors in individuals exposed to
stress rather on the stress itself. Freidman and
colleagues called the behavior pattern that is
susceptible to ischemic heart disease “Type A”.
Type A behavior is characterized by being shorttempered, aggressive, and emotionally labile,
whereas type B is described as not paying much
attention to the environment, proceeding at
one’s own pace, and being easygoing. In an
8-year follow-up survey the incidence rate of
ischemic heart disease in the subjects with a
type A behavior pattern was reported to be
double the rate in the subjects with a type B
behavior pattern.
Based on a subsequent study in the United
States and Japan an association between “anger”
and the onset of ischemic heart disease was
reported among subjects with a type A behavior pattern.6) Thus, how personality is associated with work-related factors, whether it is
an independent factor, and even its chronic
effects are unknown. Furthermore, determining whether the onset of ischemic heart disease
can be prevented by controlling these factors is
a challenge in the future.
6. Short-term overwork as a factor promoting
the onset of manifestations of
ischemic heart disease
Mental and physical overloading due to encountering unforeseeable circumstances and,
in particular, short-term excessive overloading,
cause abrupt blood pressure fluctuations, vasoconstriction, etc., with stroke and heart disease
sometimes developing, and significant increases
in sudden death and acute myocardial infarction as a result of acute stress due to unusual
events, earthquakes, etc., have been reported in
such cases.7) There is a great deal of research
evidence indicating that it is reasonable to consider the effect of unusual events that occur
between immediately before the onset and one
day before the onset or within one week before
the onset. This concept has been incorporated
into the approved criteria for death from overwork for some time.
Prevention of Ischemic Heart Disease
in Workers
1. Evaluation of work-related factors
Accumulation of fatigue as a result of working for a long period has been demonstrated to
affect the cardiovascular system medically as
well. However, it is necessary to comprehensively evaluate work-related factors that cause
stress based on work hours, irregularity of work
hours, fixed work hours, shift work, work environment, and mental strain factors originating
from the work. There is also a need for
employers and employees to cooperate in
efforts to improve working conditions, such as
shortening work time, restricting work time
outside hours, etc.3)
2. Early detection of risk factors for arteriosclerosis by regular health checkups and
correcting them
Several risk factors for arteriosclerosis are
capable of being corrected by improving one’s
lifestyle or by treatment. Workers can quit
smoking, engage in moderate exercise, consume alcoholic beverages in moderation, and
avoid overeating. Cessation of smoking has
been shown to reduce the risk of onset of
ischemic heart disease to the same level as that
of non-smokers beginning immediately after
quitting. Continuing to smoke, on the other
hand, raises the relative risk to 1.4.
Receiving regular health checkups makes it
possible to know whether risk factors are present, e.g., obesity, high blood pressure, hyperlipidemia (hypercholesterolemia, hypo-HDLcholesterolemia), abnormal glucose tolerance,
and the severity of underlying heart disease. If
risk factors are detected early, in the mildly
abnormal stage, they can be sufficiently cor-
rected by improving one’s lifestyle, and it has
even been demonstrated that a preventive
effect can be obtained by correcting them.
These factors generally contribute much more
to the onset of ischemic heart disease than
work-related factors.
It is impossible to lead a healthy happy life
while working without making efforts at selfhelp. Non-pharmaceutical therapy, such as improvement of lifestyle, improvement of diet,
etc., takes priority as a means of preventing
ischemic heart disease. The addition of drug
therapy must also be considered in patients
belonging to high-risk groups.
Wada, O.: Work and heart disease — Risk factors for “death from overwork” and preventive measures. Sangyo Igaku Review 2002; 4:
183–209. (in Japanese)
William, B. and Kannel, M.D.: Blood pressure
as a cardiovascular risk factor. JAMA 1996;
275: 1571–1576.
Ministry of Health, Labour and Welfare:
Report of the specialist committee on authorized criteria for brain and heart disease, 2001.
(in Japanese)
Rozanski, A., Blumenthal, J.A. and Kaplan, J.:
Impact of psychological factors on the pathogenesis of cardiovascular disease and implication for therapy. Circulation 1999; 99: 2192–
Karasek, K.A.: Job demands, job decision latitude and mental strain. Adm Sci Q 1979; 24:
Friedman, M.: Type A behavior: Its diagnosis,
cardiovascular relation and the effect of its
modification on recurrence of coronary artery
disease. Am J Cardiol 1989; 64: 12c–19c.
Green, W.A., Goldstein, S. and Moss, A.J.:
Psychological aspects of sudden death : a preliminary review. Arch Intern Med 1972; 129:
JMAJ, May 2004—Vol. 47, No. 5